08Aug 2018

ASSESSMENT OF THE POTENTIAL AMELIORATING EFFECTS OF BM-MSCsOR INSULIN ON THE ALTERED METABOLIC STATUS OF PANCREAS, LIVER AND KIDNEYIN STZ-DIABETIC RATS.

  • Zoology Department, Faculty of Science, Mansoura University, Egypt.
  • Zoology Department, Faculty of Science, Sylimania University, Kurdistan, Iraq.
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The current study was designed to investigate the probable hypoglycemic, hypolipidemic and hepato-renal protective effects of bone marrow derived mesenchymal stem cells (BM-MSCs) in comparison with insulin treatment in diabetic rats. Animals were classified into 4 groups; control group, diabetic group (D) received a single IP STZ dose (45 mg/kg b.w), D + insulin (0.75 IU/100 gm bw,SC daily for 4 weeks) group and D + BM-MSCs (single IV dose of 106 cell/rat). Herein, both insulin and BM-MSCs administration significantly improved the hyperglycemic status resulting from diabetes induction, as evidenced by lowered blood glucose, HbA1c and AGEs levels, while enhanced serum insulin, C-peptide and HO-1 levels, compared to the diabetic group. Regarding lipid metabolism, the increased levels of lipid fractions (TL, TG, TC and LDL-C) and the reduced HDL-C level in diabetic rats were reverted back to near normal values as a consequence to BM-MSCs treatment; indicating further, its hypolipidemic effect; in addition to enhancing the protein metabolism in diabetic rats. Furthermore, BM-MSCs was found to has hepato-renal protective effects via improving liver functions in diabetic rats; confirmed by decreased serum AST, ALT, ALP and γ-GT activities associated with decreased total bilirubin but increased total protein and albumin levels; and improving kidney status; indicated by the decreased serum levels of creatinine, uric acid and urea; compared to the diabetic group. Current findings clearly point out the health benefits of BM-MSCs; more than insulin; in ameliorating various metabolic disorders and hepato-renal diabetic complications.


  1. Abdel-Razek, H.A.D. (2010): Beneficial effect of L-Carnttine on the neuromuscular performance in diabetic rats. Menoufiya Medical Journal, 23 (2) : 159-174.
  2. Adam, S.H.; Giribabu, N.; Kassim, N.; Kumar, K.; Brahmayya, M. and Salleh, N. (2016): Protective effect of aqueous seed extract of?VitisVinifera against oxidative stress, inflammation and apoptosis in the pancreas of adult male rats with diabetes mellitus. Biomedicine and Pharmacotherapy, 81?: 439-452.
  3. Alsairafi, Z.K.; Smith, F.J.; Taylor, K.M.J.; Alsaleh, F. and Alattar, A.T. (2018): A qualitative study exploring patients? experiences regarding insulin pump use.Saudi Pharmaceutical Journal, https://doi.org/10.1016/j.jsps.2018.02.010.
  4. Amer, M.G.; Embaby, A.S.; Karam, R.A. and Amer, M.A. (2018): Role of adipose tissue derived stem cells differentiated into insulin producing cells in the treatment of type I diabetes mellitus. Gene, 654 : 87-94.
  5. Antony,?P.J.; Gandhi,?G.R.; Stalin,?A.; Balakrishna,?K. and Al-Dhabi, N.A. (2017): Myoinositol ameliorates high-fat diet and streptozotocin-induced diabetes in rats through promoting insulin receptor signaling. Biomedicine and Pharmacotherapy, 88 : 1098-1113.
  6. Arcaro, C.A.; Gutierres, V.O.; Assis, R.P.; Moreira, T.F.; Costa, P.I.; Baviera, A.M. and Brunetti, I.L. (2014): Piperine, a Natural Bioenhancer, Nullifies the Antidiabetic and Antioxidant Activities of Curcumin in Streptozotocin-Diabetic Rats. PLOS ONE, 1-27.
  7. Arya, A.; Cheaha, S.C.;Looia, C.Y.; Tahaa, H. and Mohda, M.A. (2012): The methanolic fraction of Centratherumanthelminticum seed downregulates pro-inflammatory cytokines, oxidative stress, and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats. Food and Chem. Toxicol., 50 (11) : 4209-4220.
  8. Bhansali, A.; Asokumar, P.; Walia, R.; Bhansali, S.; Gupta, V. and Jain, A. (2014): Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type II diabetes mellitus: a randomized placebo controlled study. Cell Transplant., 23 (9) : 1075-1085.
  9. Cariou, B.; Leiter, L.A.; Mu?ller-Wieland, D. Colhoun,D.M.; and Bujas-Bobanovic, M. (2017): Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk: Rationale and design of the ODYSSEY DM?INSULIN trial. Diabetes and Metabolism 43 : 453-459.
  10. Chen, C.; Cohrs, C.M.; Stertmann, J. and Speie, S. (2017): Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis. MOLECULAR METABOLISM, 6 : 943-957.
  11. Chen, Z. (2016): Adapter proteins regulate insulin resistance and lipid metabolism in obesity. Science Bulletin, 61 (19) : 1489-1497.
  12. Chien,?H.; Lee,?T.; Chen,?C.; Chiu,?Y.;Lin,?Y.; Lee, L. and Li, W. (2015): Circulating microRNA as a diagnostic marker in populations with type II?diabetes mellitus and diabetic complications. Chinese Med. Association, 78 (4) : 204-211.
  13. Christ,; Br?ckner, S. and Winkle, S. (2015): The Therapeutic Promise of MSC for Liver Restoration. Trends in Molecular Biology, 21 (11) : 673-686.
  14. Davey, G.C.; Patil, S.P.; O?Loughlin A. and O?Brien, T.(2014): Mesenchymal stem cell-based treatment for microvascular and secondary complications of Diabetes mellitus. Frontiers in Endocrinology, 5 (86) : 1-16.
  15. Davies, L.C.; Alm, J.J.; Heldring, N.; Moll, G.; Gavin, C.; Batsis, I.; Qian, H.; and Blanc, L. (2016): Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro. STEM CELLS TRANSLATIONAL MEDICINE, 5 : 1485-1495.
  16. Dewar, L. and ?Heubergerb, (2017):?The effect of acute caffeine intake on insulin sensitivity and glycemic control in people with diabetes. Diabetes and Metabolic Syndrome:https://doi.org/10.1016/j.dsx.2017.04.017.
  17. El Barky, A.R.;??Ezz, A.A, and?Alm-Eldeen, A.A. (2018): Can Stem Cells Ameliorate the Pancreatic Damage Induced by Streptozotocin in Rats?Canadian Journal of Diabetes, 42 (1)?: 61-70.
  18. El-Kholy, W.M.; El-Habibi, E.M. and El-Sawah, S.G. (2011): The ameliorating effect of Aloe vera gel extract on the altered metabolic and antioxidant status in streptozotocin-diabetic rats. Egypt. Ger. Soc. Zool. J., 63A: Comparative physiology : 133-154.
  19. Elmarakby, A.; Faulkner, J.; Saleh, M.A. and Sullivan, J.C. (2012): Induction of hemeoxygenase-1 reduces glomerular injury and apoptosis in diabetic spontaneously hypertensive rats. Am J Physiol Renal Physiol., 302 : 791-800.
  20. El-Sharaky, A.S.; Newairy, A.A.; Badreldeen, M.M.; Eweda, S.M. and Sheweita, S.A. (2007): Protective role of selenium against renal toxicity induced by cadmium in rats. Toxic. J., 235 : 185-193.
  21. Ene, A.; Nwankwo, E. and Samdi, L. (2007): Alloxan-induced diabetes in rats and the effects of black caraway (Carumcarvi l.) oil on their body weight. Res. J. Medic. Med. sciences, 2 (2) : 48 ? 52.
  22. Fang, Y.; Tian, X.; Bai, S.; Hou, W. and Tong, H. (2012): Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induce diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38MAPK signaling pathway. Int J Mol Med., 30 : 85-92.
  23. Fathi-Kazerooni, M.; Tavoosidana, G.; Khanjani, S.; Edalatkhah, H. and Kazemnejad, S. (2017): Comparative restoration of acute liver failure by menstrual blood stem cells compared with bone marrow stem cells in mice model. Cytotherapy, 19 (12) : 1474-1490.
  24. Feig, D.I.; Kang, D. and Johnson, R.J. (2008): Uric acid and cardiovascular risk. N Engl J Med., 359 : 1811-1821.
  25. Gao, D.; Xie, J.; Zhang, J.; Feng, C.; Yao, B.; Ma, K.; Li, J.; Wu, X.; Huang, S. and Fu, X. (2014): MSC attenuate diabetes-induced functional impairment in adipocytes via secretion of insulin-like growth factor-1. Biochemical and Biophysical Research Communications, 452 (1) : 99-105.
  26. Ghosh, S.; Bhattacharyya, S.; Rashid, K. and Sil, P. (2015): Curcumin protects rat liver from streptozotocin-induced diabetic pathophysiology by counteracting reactive oxygen species and inhibiting the activation of p53 and MAPKs mediated stress response pathways. Tox. Rep. J., 2 : 365-376.
  27. Giralt, A.; Denechaud, P.; Lopez-Mejia, I.C.; Bonner, C.; Pattou, F.; Annicotte, J. and Fajas, L. (2018): E2F1 promotes hepatic gluconeogenesis and contributes to hyperglycemia during diabetes. Molecular Metabolism, doi: 10.1016/j.molmet.2018.02.011.
  28. Gougeon, R. (2013): Insulin Resistance of Protein Metabolism in Type 2 Diabetes and Impact on Dietary Needs: A Review. Canadian Journal of Diabetes, 37 (2) ; 115-120.
  29. Hamza, A.H.; Al-Bishri, W.M.; Damiati, L.A. and Ahmed, H.H. (2016): Mesenchymal stem cells: a future experimental exploration for recession of diabetic nephropathy. RENAL FAILURE, 39 (1) : 67-76.
  30. Hebert, S.L. and Nair, K.S. (2010): Protein and energy metabolism in type 1 diabetes. Clinical Nutrition, 29 (1) : 13-17.
  31. Herman, M.E.; O'Keefe, J.H.; Bell, D.S.H. and Schwartz, S.S. and (2017): Insulin Therapy Increases Cardiovascular Risk in Type 2 Diabetes. Progress in Cardiovascular Diseases, 60 (3) : 422-434.
  32. Huynh, K.; Bernardo, B.C.; McMullen, J.R. and Ritchie, R.H. (2014): Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacology and therapeutics, 142 : 375-415.
  33. Jaen, M.L.; Vil?, L.; Elias, I.; Jimenez, V.; Rod?, J.; Haurigot, V. and Bosch, F. (2017): Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs. Molecular Therapy: Methods and Clinical Development, 6 : 1-7.
  34. James, H.A.; O'Neill, B.T. and Nair, K.S. (2017): Insulin Regulation of Proteostasis and Clinical Implications. Cell Metabolism, 26 (2) : 310-323.
  35. Jamshidi, M.; Ziamajidi, N.; Khodadadi, I.; Dehghan, A. and Kalantarian, G. (2018): The effect of insulin-loaded trimethylchitosan nanoparticles on rats with diabetes type I. Biomedicine and Pharmacotherapy, 97 : 729-735.
  36. Jiang, Z.; Liu, Y.; Niu, X.; Yin, J.; Hu, B.; Guo, S.; Fan, Y.; Wang, Y. and Wang, N. (2016): Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats. Stem Cell Research and Therapy, 7 : 24-37.
  37. Kalirai, S.; Stephenson, J.; Perez-Nieves, M.; Reeda, B. and Fisher, L. (2017): Primary care physician perspectives on basal insulin initiation and maintenance in patients with type 2 diabetes mellitus. Primary Care Diabetes, 648 : 1-8.
  38. Katz, L.E.; Bacha, F.; Gidding, S. and Marcovina, S. (2018): Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes. The Journal of Pediatrics, In Press.
  39. Koppe, L.; Nyam, E. and Vivot, K. (2016): Urea impairs beta cell glycolysis and insulin secretion in chronic kidney disease. J Clin Invest., 126 : 3598-3612.
  40. Koroglu, , P.; Senturkb, G.E.; Yucela, D.; Ozakpinarc, O.B.; Urasc, F. and Arbaka, S. (2015): The effect of exogenous oxytocin on streptozotocin (STZ)-induced diabetic adult rat testes. Peptides, 63 : 47-54.
  41. Krijnen, P.A.J.; Simsek, S. and Niessen, H.W.M. (2009): Apoptosis in diabetes. Apoptosis, 14 : 1387-1388.
  42. Kumar, A.; Pati, N. and Sarin, S. (2011): Use of Stem Cells for Liver Diseases: Current Scenario. Journal of Clinical and Experimental Hepatology, 1 (1) : 17-26.
  43. Lee, C.; Chen, Y.F.; Wu, H.H. and Lee, O,K, (2018): Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases. Gastroenterology, 154 (1) : 46-56.
  44. Li, L.; Li, F.;?Gao, F.;?Yang, Y.;?Liu, Y.;?Guo, P. and?Li, Y. (2016): Transplantation of mesenchymal stem cells improves type 1 diabetes mellitus. Cell and Tissue Research, 364 (2)?: 345-355.
  45. Li, W.; Cavelti-Weder, C.; Zhang, Y.; Clement, K.; Donovan, S.; Gonzalez, G.; Zhu, J.; Stemann, M.; Zeng, S.; Meissner, A.; Weir, G. and Zhou, Q. (2014): Long-term persistence and development of induced pancreatic beta cells generated by lineage conversion of acinar cells. Nat Biotechnol, 32 : 1223-1230.
  46. Li, X.;? Li, H.;Lub,?N.; Feng, Y.; Huang,?Y. and ?Gao, Z. (2012): Iron increases liver injury through oxidative/nitrative stress in diabetic rats: Involvement of nitrotyrosination of glucokinase. Biochimie, 94 (12) : 2620?2627.
  47. Lin, D.; Qi, Y.; Huang, C.; Wu, M.; Wang, C.; Li, F.; Yang, C.; Yan, L. Ren, M. and Sun, K. (2017): Associations of lipid parameters with insulin resistance and diabetes: A population-based study. Clinical Nutrition, In Press.?
  48. Lin,Y.; Chen, C.Y.; Wu, S.C. and Din, S.T. (2013): Modulation of glucose and lipid metabolism by porcine adiponectin receptor 1?transgenic mesenchymal stromal cells in diet-induced obese?mice. Cytotherapy, 15 (8) : 971-978.
  49. Liu, X.; Zheng, P.; Wang, X.; Cheng, H. and Zhang, Z. (2014): A preliminary evaluation of efficacy and safety of Wharton?s jelly mesenchymal stem cell transplantation in patients with type II diabetes. Cell Res Ther., 5 (2) : 57-66.
  50. Lu, J.; Xia, Q. and Zhou, Q. (2017): How to make insulin-producing pancreatic β cells for diabetes treatment. Sci China Life Sci, 60 : 239-248.
  51. Lv, S.S.; Liu, G.; Cheng, J. and Sun, A.L. (2013): MSCs transplantation ameliorates glomerular injury in streptozotocin- induced diabetic nephropathy in rats via inhibiting macrophage infiltration. Int Immunopharmacol., 17 : 275-282.
  52. Manjusha; Aggarwala, N.; Niteshb and Guptac, P. (2012): Effect of petroleum ether extract of Sesbaniasesban (Merr.) roots in streptozotocin (STZ) induced diabetes in mice. Asian Pacific J. of Tropical Biomed., 2 (3) : 1254?1260.
  53. Mayyas, F.; Jaradat, R. and Alzoubi, K.H. (2018): Cardiac effects of fish oil in a rat model of streptozotocin-induced diabetes. Nutrition, Metabolism and Cardiovascular Diseases, In Press.
  54. Miyata, T. and Dan, T. (2012): Inhibition of advanced glycation end products (AGEs): An implicit goal in clinical medicine for the treatment of diabetic nephropathy? Diabetes Res Clin Pract., 82 (1) : 25-29.
  55. Mohan, and Nandhakumar, L. (2014): Role of various flavonoids: Hypotheses on novel approach to treat diabetes. Med. Hypotheses and Ideas., 8 (1) : 1-6.
  56. Monfrinia, M.;??Donzelli,?E.; Rodriguez-Menendez,?V.; Oggioni,?N. and Crippa, L. (2017): Therapeutic potential of Mesenchymal Stem Cells for the treatment of diabetic peripheral neuropathy Experimental Neurology, 288 : 75-84.
  57. Muruganathan, U.; Srinivasan, S. and Vinothkumar, V. (2017): Antidiabetogenic efficiency of menthol, improves glucose homeostasis and attenuates pancreatic β-cell apoptosis in streptozotocin?nicotinamide induced experimental rats through ameliorating glucose metabolic enzymes. Biomedicine and Pharmacotherapy, 92,?: 229-239.
  58. Nagaishi, K.;?Ataka, K.;?Echizen, E. and?Fujimiya, M. (2014): Mesenchymal stem cell therapy ameliorates diabetic hepatocyte damage in mice by inhibiting infiltration of bone marrow-derived cells. Hepatology,59 (5) : 1816-1829.
  59. Newairy, A.A.; Salama, A.F.; Hussien, H.M. and Yousef, M.I. (2009): Propolis alleviates aluminium-induced lipid peroxidation and biochemical parameters in male rats. Food and Chem. Toxic. J., 47 : 1093-1098.
  60. Nia, P.H.;?Khorram, S.;?Rezazadeh, H.;?Safaiyan, A. and?Tarighat-Esfanjani, A. (2018):? The Effects of Natural Clinoptilolite and Nano-Sized Clinoptilolite Supplementation on Glucose Levels and Oxidative Stress in Rats with Type 1 Diabetes. Canadian Journal of Diabetes, 42 (1)?: 31-35.
  61. Ning, H.; Sun, Z.; Liu, Y.; Liu, L.; Hao, L.; Chu, Y.; Li, S. and Sun, C. (2016): Insulin Protects Hepatic Lipotoxicity by Regulating ER Stress through the PI3K/Akt/p53 Involved Pathway Independently of Autophagy Inhibition. Nutrients, 8 : 227-249.
  62. Oche, O.;? Sani,?I.; Chilaka, N.G.;? Samuel, N.U. and? Samuel, A. (2014): Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of?Vitex doniana?in normal and streptozotocin-induced diabetic albino rats. Asian Pac. Trop. Biomed. J., 4(2) : 124?130.
  63. Petit, J.M. (2017): Special features of diabetes associated with liver diseases. M?decine des Maladies M?taboliques, 11 (8) : 682-686.
  64. Pitlovanciv, E.; Fernandes, G.S. and Teixeira, L.C. (2013): Hemeoxygenase 1 improves glucose metabolism and kidney histological alteration in diabetic rats. DiabetolMetabSyndr., 5 : 3-16.
  65. Qi, k.; Li. N. and Melino, G. (2017): Tissue regeneration: The crosstalk between mesenchymal stem cells and immune response. Cellular Immunology, In Press.
  66. Ramanathan,; Rupert, S.; Selvaraj, S.; Satyanesan, J.; Vennila, R. and Rajagopa, S. (2017): Role of Human Wharton's Jelly Derived Mesenchymal Stem Cells (WJ-MSCs) for Rescue of?d-Galactosamine Induced Acute Liver Injury in Mice. Journal of Clinical and Experimental Hepatology,7 (3) : 205-214.
  67. Ramesh, B.; Karuna, R.; Sreenivasa, R.S.; Sasi, B.R.B. and Saralakumari, D. (2012): Effect of Commiphoramukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats. Asian Pac J Trop Biomed., 2 (11) : 895-900.
  68. Roche, E.; Ense?at-Waser, R.; Reig, J.A.; Jones, J. and Le?n-Quinto, T. (2017): Therapeutic Potential of Stem Cells in Diabetes. Handbook of Experimental Pharmacology, 174 : 147-167.
  69. Rookmaaker, M.B.; Verhaar, M.C. and De Boer H. (2007): Met-RANTES reduces endothelial progenitor cell homin to activated (glomular) endothelium in vitro and in vivo. Am J Physiol Renal Hysiol., 293 : 624-630.
  70. Si, Y.; Zhao, Y.; Hao, H.; Liu, J.; Guo, Y. and Mu, Y.(2017): Infusion of mesenchymal stem cells ameliorates hyperglycemia in type II diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes, 61 (6) : 1616-1625.
  71. Singh, J. and Kakkar, P. (2013): Modulation of liver function, antioxidant responses, insulin resistance and glucose transport by Oroxylumindicum stem bark in STZ induced diabetic rats. Food and Chem. Tox., 62 : 722-731.
  72. Sirasanagandla, S.: BabuKasetti, R.B.;Cirradur, S.R. and Chippada, A. (2013): Antihyperglycemic and antihyperlipidemic activities of 2-(4-[(2-hydroxybenzyl) amino]-phenyl amino-methyl)-phenol in STZ induced diabetic rats. Europ. Medicin. Chem. J., 66 : 400-406.
  73. Sood, V.; Mittal, B.R.; Bhansali, A.; Singh, B.; Khandelwal, N. and Marwaha, N. (2015): Biodistribution of 18F-FDG-labeled autologous bone marrow-derived stem cells in patients with type II diabetes mellitus: exploring targeted and intravenous routes of delivery. Clin Nucl Med., 40 (9) : 697-700.
  74. Sordia,?V.;Pellegrinia,?S.;Kramperab,?M.;Pant?h,?G. and Piemonti, L. (2017): Stem cells to restore insulin production and cure diabetes. Nutrition Metabolism and Cardiovascular Diseases, org/10.1016/j.numecd.2017.02.004
  75. Subramanian, S. and Hirsch, I.P. (2018): Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes Mellitus. Endocrinology and Metabolism Clinics of North America, 47 (1) : 65-79.
  76. Tabara,?Y.; Arai,?H.;Hirao,?Y.; Takahashi,?Y. andMatsud, F. (2017): Different inverse association of large high-density lipoprotein subclasses with exacerbation of insulin resistance and incidence of type 2 diabetes: The Nagahama study. Diabetes Research and Clinical Practice, 127 : 123-131.
  77. Thakkar, U.G.; Vanikar, A. and Trivedi, H.L. (2017): Should we practice stem cell therapy for type 1 diabetes mellitus as precision medicine? Cytotherapy, 19 : 574-576.
  78. Thakkar, U.G.;?Trivedi, H.L. and Dave, S.D.?(2016): Co-infusion of insulin-secreting adipose tissue-derived mesenchymal stem cells and hematopoietic stem cells: novel approach to management of type I diabetes mellitus. International Journal of Diabetes in Developing Countries, 36 (4) : 426-432.
  79. Thomas, S.S.; Zhang, L. and Mitch, W.E. (2015): Molecular mechanisms of insulin resistance in chronic kidney disease. Kidney Int., 88 : 1233-1239.
  80. Wang, S.; Li, Y.; Zhao, J.; Zhang, J. and Huang, Y. (2013): Mesenchymal stem cells ameliorate podocyte injury and proteinuria in a type 1 diabetic nephropathy rat model. Biol Blood Marrow Transplant., 19 : 538-546.
  81. Wang, Y.; Chen, X.; Cao, W. and Shi, Y. (2014): Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol., 15 (11) : 1009-1016.
  82. Wang, Y.;?Yan,?J.; Zou,?X.; Guo, K.;?Zhao,?Y.; Meng,?C.; Yin,?F. and Guo,?L. (2017): Bone marrow mesenchymal stem cells repair cadmium-induced rat testis injury by inhibiting mitochondrial apoptosis. Chemico-Biological Interactions, 271 : 39-47.
  83. Wang, Z.; ?Cao,?J.; Li,?D.; Zhang,?X.; Liu,?J.; Li,?J.; Wang, M.; ?Liu,?Y.; Xu,?B. and Wang, H. (2015): Clinical efficacy of autologous stem cell transplantation for the treatment of patients with type II diabetes mellitus: a meta-analysis. Cytotherapy, 17 (7) : 956-968.
  84. Xie, M.; Chena, D.; Zhanga, F.; Willskyb, G.R.; Cransc, D.C and Ding, W. (2014): Effects of vanadium (III, IV, V)-chlorodipicolinate on glycolysis and antioxidant status in the liver of STZ-induced diabetic rats. Biochem. J., 136 : 47-56.
  85. Xie, Y.; Bowe, B.; Li, T.; Hong, X.; Yan, Y. and Al-Aly, Z. (2018): Higher blood urea nitrogen is associated with increased risk of incident diabetes mellitus. Kidney International, 93 : 741-752.
  86. Xv, J.; Ming, Q.; Wang, X.; Zhang, W.; Li, Z.; Wang, S.; Li, Y. and Li, L. (2017): Mesenchymal stem cells moderate immune response of type 1 diabetes. Cell and Tissue Research, 368 (2) : 239-248.
  87. Yener, S.; Comlekci, A. and Akinci, B. (2008): Serum transforming growth factor-beta I levels in normoalbuminuric and normotensive patients with type 2 diabetes. Effect of metformin and rosiglitazone. Hormones, 7 : 70-76.
  88. Zang, L.; Hao, H.; Liu, J.; Han W. and Mu, Y. (2017): Mesenchymal stem cell therapy in type II diabetes mellitus. Diabetology Metabolic Syndrome, 9 (36) : 1-11.
  89. Zhang, C.; Wang, T.; Ma, J.; Liu, Y. and Wang, D. (2017): Protective effect of CDDO-ethyl amide against high-glucose-induced oxidative injury via the Nrf2/HO-1 pathway. The Spine Journal, 17 (7) : 1017-1025.
  90. Zhou, J.; Zhang, Z. and Qian, G. (2016): Mesenchymal stem cells to treat diabetic neuropathy: A long and strenuous way from bench to the clinic. Cell Death Discovery, 2 : e16055; doi:10.1038/cddiscovery.

[Wafaa M. El-Kholy, Reda H. Hussein and Dlovan Y. Khalil (2018); ASSESSMENT OF THE POTENTIAL AMELIORATING EFFECTS OF BM-MSCsOR INSULIN ON THE ALTERED METABOLIC STATUS OF PANCREAS, LIVER AND KIDNEYIN STZ-DIABETIC RATS. Int. J. of Adv. Res. 6 (Aug). 18-34] (ISSN 2320-5407). www.journalijar.com


Shady Gamal


DOI:


Article DOI: 10.21474/IJAR01/7487      
DOI URL: http://dx.doi.org/10.21474/IJAR01/7487